Plasmodium falciparum is the most lethal pathogen among four species of Plasmodium that infect human beings.1 The immunosuppressive drug FK506 shows an antimalarial effect,2 suggesting that the parasite may contain a potential FK506 binding protein (FKBP) as the molecular target of the drug. Database analysis revealed the presence of a putative peptidylprolyl cis-trans isomerase (PPIase) (Swiss-Prot/TremBL ID Q8I4V_PLAF7) in Plasmodium falciparum. Recent studies have named it Plasmodium falciparum FKBP35 (PfFKBP35; GeneBank accession no. AAN36539) as a member of the FKBP family in the parasite.3,4 PfFKBP35 shows a high similarity to FKBP12 in the catalytic core domain [40% sequence identity, Fig. 1(A)], whereas the overall structural architecture resembles the multiple tetratricopeptide repeat-containing FKBP family including FKBP38, FKBP51, and FKBP52.7 FKBP family, which is a part of a larger superfamily of immunophilins exerting roles as chaperones and possessing PPIase, plays important roles in several cellular processes including protein folding and suppressing T-cell activation upon binding the immunosuppressive ligands.8 Currently, little is know about how the growth of the parasite is inhibited by FK506. To better understand the biological function of PfFKBP35 and also provide a basis of the molecular interaction between PfFKBP35 and the ligand, in this study, we have determined the solution structure of the core isomerase domain PfFKBP35 (referred hereafter as FKBD). The structure shows the similar folds as seen in the other FKBP family proteins. Differences were seen in the regions of b3/4 and b5/6 loops, which are important for ligand-binding and PPIase activities. MATERIALS AND METHODS